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Obstetrics

Rhesus Disease (Haemolytic Disease of the Fetus and Newborn)

Rhesus disease is haemolytic disease of the fetus and newborn caused by maternal IgG alloantibodies crossing the placenta and destroying fetal red cells carrying the corresponding antigen; anti-D disease is largely preventable, whereas established sensitisation requires specialist fetal and neonatal surveillance.

In a nutshell

Rhesus disease is HDFN caused by maternal IgG alloantibodies, classically anti-D, causing fetal anaemia and postnatal haemolysis. Prevent sensitisation in eligible non-sensitised D-negative people with anti-D prophylaxis and use targeted fetal-RHD screening where available. Established alloimmunisation requires antibody-specific monitoring, fetal antigen assessment and fetal-medicine MCA Doppler; MCA PSV above 1.5 MoM or other signs of anaemia requires specialist review. Neonatal jaundice in the first 24 hours is an emergency signal and treatment follows NICE age- and gestation-specific bilirubin graphs.

Classic presentation

A D-negative pregnant person has immune anti-D and a fetus predicted to be D-positive. Arrange fetal-medicine surveillance with serial antibody assessment and MCA Doppler. If the newborn develops jaundice in the first 24 hours, obtain urgent serum bilirubin, haemoglobin, blood group and DAT and involve neonatology.

Key points

  • Maternal IgG anti-D, anti-c, anti-K and other antibodies can cross the placenta and cause fetal anaemia; anti-D is preventable but established immune anti-D is not reversed by prophylaxis.
  • A first pregnancy is not automatically protected: prior pregnancy, transfusion or an earlier sensitising event may have caused alloimmunisation.
  • Routine antenatal anti-D is for eligible non-sensitised D-negative people; it is still needed with non-D antibodies but not when immune anti-D is established.
  • NHSBT fetal-RHD screening uses cell-free fetal DNA to guide prophylaxis in non-sensitised D-negative people and is not a diagnostic test for immune anti-D or anti-G.
  • MCA PSV above 1.5 MoM or other ultrasound signs of fetal anaemia requires urgent fetal-medicine assessment for possible intrauterine transfusion.
  • Jaundice in the first 24 hours is pathological until assessed; use NICE bilirubin graphs, intensive phototherapy and escalation to IVIG or exchange transfusion when indicated.

First-line investigation

Maternal booking and 28-week blood group and antibody screen, followed by antibody identification and specialist fetal-antigen and fetal-medicine assessment when clinically significant antibodies are present.

Management

Identify antibodies and risk

  • Confirm maternal blood group, antibody specificity, passive versus immune anti-D, relevant fetal antigen status and previous HDFN history; involve transfusion medicine and fetal medicine early.3,6

Prevent avoidable sensitisation

  • Give routine, event-related and postnatal anti-D according to eligibility and current local protocol; use fetal-RHD screening to target routine prophylaxis where implemented.2,6,8

Monitor for fetal anaemia

  • Follow antibody-specific testing and use serial MCA Doppler when the fetus is at risk; escalate urgently if MCA PSV exceeds 1.5 MoM, hydrops develops or fetal wellbeing deteriorates.3,4

Treat the fetus or newborn in the right service

  • Use specialist intrauterine transfusion or planned birth when indicated, alert neonatology, and manage neonatal bilirubin and anaemia with NICE thresholds, phototherapy, selected IVIG or exchange transfusion.3,5,1

Exam traps

  • Do not say that every first RhD-positive pregnancy is unaffected; sensitisation may predate the pregnancy.
  • Do not give anti-D as treatment for established immune anti-D, but do not withhold it from an eligible D-negative person with non-D antibodies.
  • Do not interpret a positive DAT without considering maternal prophylactic anti-D and the clinical picture.
  • Do not use an isolated antibody titre or a normal scan to rule out fetal anaemia; use the antibody-specific pathway and MCA Doppler.
  • Do not use a generic bilirubin threshold or visual inspection alone for neonatal jaundice.
  • Do not perform intrauterine transfusion outside a specialist fetal-medicine service.

Illustrations

Hydrops fetalis on ultrasoundFetal axial ultrasound showing diffuse subcutaneous oedema and fluid accumulation consistent with hydrops fetalis, a severe possible consequence of fetal anaemia.Nevit Dilmen, Wikimedia Commons · CC-BY-SA-3.0

Key sources

  1. NHS, Haemolytic disease of the fetus and newborn (HDFN) (NHS patient information last reviewed 20 March 2026: causes, antenatal screening, fetal and neonatal treatment and safety-netting)Updated 20 Mar 2026
  2. NICE TA156, Routine antenatal anti-D prophylaxis for women who are rhesus D negative (Current NICE technology appraisal recommendation: routine antenatal anti-D options and the population eligible for prophylaxis; published 2008)Updated 27 Aug 2008
  3. RCOG Green-top Guideline No. 65, The management of women with red cell antibodies during pregnancy (RCOG guidance published 2014 and listed as archived: antibody identification, monitoring, fetal antigen status, MCA Doppler, referral and intrauterine transfusion principles)Updated 1 May 2014
  4. RCOG Scientific Impact Paper No. 75, The use of novel therapies in the management of HDFN (RCOG scientific impact paper: HDFN pathophysiology, fetal anaemia, intrauterine transfusion and neonatal consequences; use for context alongside current clinical guidance)
  5. NICE CG98, Jaundice in newborn babies under 28 days (NICE neonatal jaundice guidance last updated 31 October 2023: early jaundice assessment, DAT interpretation, bilirubin treatment graphs, IVIG and exchange transfusion)Updated 31 Oct 2023
  6. NHS Blood and Transplant, Fetal RHD screening service (Current NHSBT service information: cell-free fetal DNA prediction for D-negative non-sensitised women, limitations in immune anti-D or anti-G and UK implementation details)
  7. NICE HTG420, High-throughput non-invasive prenatal testing for fetal RHD genotype (NICE diagnostics guidance supporting cell-free fetal DNA fetal-RHD testing to guide antenatal anti-D prophylaxis; published 2017)Updated 27 Sept 2017
  8. BNF, current anti-D immunoglobulin and neonatal prescribing information (UK prescribing reference for product selection, contraindications and dosing; direct access was restricted in this review and unsupported product-specific details were deferred to BNF and local transfusion protocol)

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.